Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are sophisticated modalities typically used in the second-line diagnosis following routine clinical practice. Among them, CT is regarded as the standard imaging in diagnosing pancreatic cancer at present in Japan due to its popularity and reasonable reliability in wide-ranging diagnostic ability. However, even with multidetector row CT (MDCT), the demonstration of pancreatic cancer less than 1 cm in size remains nearly impossible. CT staging is considered accurate in one-half to two-thirds of patients, but limitations in the imaging of peripancreatic microinvasion and nodal or hepatic micrometastases still have a tendency to underestimate tumor extension. With recent advancement in imaging techniques, MRI has proven to be equal or superior to other imaging modalities in diagnosing pancreatic cancer. Most of all, it is expected that MRCP will become as effective an instrument as ultra-sonography (US) in the screening of pancreatic cancer. Functional imaging with PET using the glucose analog FDG can be used in the diagnosis of pancreatic cancer, but systemic or local disturbance of glucose metabolism may result in an incorrect diagnosis. The usefulness of PET is now considered in assessing tumor viability, monitoring tumor response to treatment, and detecting distant metastases.     

Positron emission tomography and molecular imaging

The use of positron emission tomography (PET) in cardiology is growing rapidly. Technical features make PET a strong technology for the non-invasive evaluation of cardiac physiology. It is currently considered the most reliable tool for the identification of myocardial viability and also allows accurate assessment of myocardial perfusion and detection of coronary artery disease (CAD). The unique feature of PET is that myocardial perfusion can be measured in absolute terms, improving sensitivity in the detection of multivessel of disease and also allowing evaluation of very early changes in coronary vasoreactivity and the progression or regression of CAD. Use of the newest generation of PET systems with integrated multislice computed tomography (CT) is becoming a standard technique for cardiac imaging. Since the PET and CT techniques ideally complement each other the combination is particularly attractive for the non-invasive assessment of CAD but also has other functions. Finally, there are also promising future applications that involve molecular imaging of cardiac targets, which may further enhance the clinical utility of PET and hybrid imaging.     

Vascular imaging with positron emission tomography

Atherosclerosis is an inflammatory disease that causes most myocardial infarctions, strokes and acute coronary syndromes. Despite the identification of multiple risk factors and widespread use of drug therapies, it still remains a global health concern with associated costs. Although angiography is established as the gold standard means of detecting coronary artery stenosis, it does not image the vessel wall itself, reporting only on its consequences such as luminal narrowing and obstruction. MRI and computed tomography provide more information about the plaque structure, but recently positron emission tomography (PET) imaging using [(18) F]-fluorodeoxyglucose (FDG) has been advocated as a means of measuring arterial inflammation. This results from the ability of FDG-PET to highlight areas of high glucose metabolism, a feature of macrophages within atherosclerosis, particularly in high-risk plaques. It is suggested that the degree of FDG accumulation in the vessel wall reflects underlying inflammation levels and that tracking any changes in FDG uptake over time or with drug therapy might be a way of getting an early efficacy readout for novel anti-atherosclerotic drugs. Early reports also demonstrate that FDG uptake is correlated with the number of cardiovascular risk factors and possibly even the risk of future cardiovascular events. This review will outline the evidence base, shortcomings and emerging applications for FDG-PET in vascular imaging. Alternative PET tracers and other candidate imaging modalities for measuring vascular inflammation will also be discussed.     

Quantitative single-photon emission computed tomography imaging

Over the past decade, quantitation of cardiac single-photon emission computed tomography (SPECT) data, once limited to perfusion assessment, has been extended to global and regional function assessment for both the left and the right ventricle, as well as to measurement of additional cardiac parameters of diagnostic and prognostic interest. A number of commercially available quantitative algorithms exist, based on different mathematic operators and with varying degrees of automation, that are capable of providing accurate and reproducible results. This article describes the many quantitative cardiac SPECT measurements available today, defining them in terms of validation, practical use, and limitations.     

Positron emission tomography and computed tomography versus positron emission tomography computed tomography: tools for imaging the lung

This article reviews the potential use of positron emission tomography (PET), alone and in combination with computed tomography, for evaluating the severity of disease in cystic fibrosis. PET scanning using injected 18F-fluorodeoxyglucose provides visual and quantitative information for the rate at which glucose is taken up by the lung, a process that should relate to the presence of inflammation and reflect the extent of the disease. The computed tomography scan gives highly accurate density and anatomic information to locate areas of inflammation seen on the PET scan, increasing the accuracy of the interpretation. Until recently, the scanners have been single systems, often located in separate hospital departments. Combined systems are now commercially available, with major advantages for patients and in the quality of analytical information obtained for interpretation by the physician. The use of 18F-fluorodeoxyglucose uptake and PET scanning has been suggested as a biomarker of progressive pulmonary inflammation in cystic fibrosis. Although promising, the data so far are limited. Further studies will be needed to validate this measurement for this purpose.     

Positron emission tomography imaging in the thorax

Positron emission tomography imaging has proven valuable in the evaluation and management of thoracic abnormalities. It is more accurate than CT or MR imaging in characterizing indeterminate focal abnormal pulmonary opacities, staging lung cancer, and assessing the therapeutic response. PET imaging in lung cancer also appears to be cost-effective, particularly with whole-body studies. The metabolic and physiologic abnormalities used in FDG-PET imaging, rather than conventional anatomic or morphologic characteristics, provide an invaluable model for the future of tumor imaging.     

Hepatic imaging: positron emission tomography, digital angiography, and nuclear magnetic resonance imaging

Major advances in diagnostic imaging of the human body have been made in recent years. Positron emission tomography, a technique founded on advances in radiopharmaceuticals and radionuclide imaging apparatus, permits imaging regional metabolism, metabolite distribution, and flow. Thus far, its major applications have been in the study of the brain, and to a lesser extent, the heart; however, it is also finding a role in the study of the liver. Digital angiography is being applied to fluoroscopic systems which permits visualization of relatively low doses of intravascular iodinated radiographic contrast media. Imaging of the major arteries is possible using simple intravenously administered contrast media; digital techniques also increase the diagnostic yield in intraarterial studies. Nuclear magnetic resonance (NMR) imaging is an outgrowth of laboratory NMR spectroscopy; the interaction of radiofrequency signals with nuclei in strong magnetic fields permits imaging the distribution and certain chemical properties of various isotopes. Hydrogen NMR imaging is proving most useful for clinical diagnosis. The techniques used to image hydrogen are also being applied to NMR spectroscopy in vivo of various isotopes, including carbon-13, phosphorus-31, and hydrogen-1.     

The role of positron emission tomography in gastrointestinal imaging

Although the use of PET in studies of the gastrointestinal tract is still relatively new, its value is clear. The future will provide a better definition of the indications for PET, refinement of the technology, and its relative value compared with other modalities such as peptide and antibody imaging, CT, MR imaging, and US.     

Positron emission tomography provides molecular imaging of biological processes

Diseases are biological processes, and molecular imaging with positron emission tomography (PET) is sensitive to and informative of these processes. This is illustrated by detection of biological abnormalities in neurological disorders with no computed tomography or MRI anatomic changes, as well as even before symptoms are expressed. PET whole body imaging in cancer provides the means to (i) identify early disease, (ii) differentiate benign from malignant lesions, (iii) examine all organs for metastases, and (iv) determine therapeutic effectiveness. Diagnostic accuracy of PET is 8-43% higher than conventional procedures and changes treatment in 20-40% of the patients, depending on the clinical question, in lung and colorectal cancers, melanoma, and lymphoma, with similar findings in breast, ovarian, head and neck, and renal cancers. A microPET scanner for mice, in concert with human PET systems, provides a novel technology for molecular imaging assays of metabolism and signal transduction to gene expression, from mice to patients: e.g., PET reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. PET probes and drugs are being developed together-in low mass amounts, as molecular imaging probes to image the function of targets without disturbing them, and in mass amounts to modify the target's function as a drug. Molecular imaging by PET, optical technologies, magnetic resonance imaging, single photon emission tomography, and other technologies are assisting in moving research findings from in vitro biology to in vivo integrative mammalian biology of disease.     

Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

2-[(18)F]Fluoro-2-deoxy-d-glucose positron emission tomography ([(18)F]FDG PET) detection of the up-regulated glycolysis associated with malignant transformation is a noninvasive imaging technique used extensively in cancer diagnosis. Although striking similarities exist in glucose transport and metabolism between tumor cells and activated immune cells, the potential use of [(18)F]FDG PET for the diagnosis and evaluation of autoimmune disorders has not been systematically investigated. Here we ask whether [(18)F]FDG PET in conjunction with computed tomography (CT) could be used to monitor a complex autoimmune disorder such as murine experimental autoimmune encephalomyelitis (EAE) and whether this approach is sensitive enough to evaluate therapeutic interventions. We found that (i) coregistration of metabolic (i.e., microPET) and high-resolution anatomical (i.e., CT) images allows serial quantification of glycolysis with [(18)F]FDG in various spinal column segments; (ii) [(18)F]FDG PET/CT can detect the increased glycolysis associated with paralysis-causing inflammatory infiltrates in the spinal cord; and (iii) the [(18)F]FDG measure of glycolysis in the spinal cord is sensitive to systemic immunosuppressive therapy. These results highlight the potential use of serial [(18)F]FDG PET/CT imaging to monitor neuroinflammation in EAE and suggest that similar approaches could be applied to the diagnosis and evaluation of other autoimmune and inflammatory disorders in animal models and in humans.     

Usefulness of combined positron emission tomography and computed tomography imaging in Erdheim-Chester disease

INTRODUCTION: Erdheim-Chester disease is a rare non-Langerhans form of histiocytosis. We report the use of combined fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) in this disease. EXEGESIS: Three men, aged from 55 to 74 years with confirmed Erdheim-Chester disease were included. 18F-FDG PET-CT allowed to detect visceral and vascular involvement of the disease which were overlooked with CT-scan or magnetic resonance imaging: left common carotid and ilio-femoral artery in one patient, coronary, femoral and tibia in the second, aortic, common carotid, femoral and mandibula in the remaining patient. Also, sequential 18F-FDG PET-CT was useful to appreciate treatment efficiency (decrease hyperfixation) and decide treatment modification (interferon alpha). CONCLUSION: 18F-FDG PET-CT combined imaging allows to assess the extent of involvement in Erdheim-Chester disease. 18F-FDG PET-CT may be also a useful tool in the management of Erdheim-Chester disease.     

Major advances in single-photon emission computed tomography perfusion imaging

Major advances in single-photon emission computed tomography (SPECT) myocardial perfusion imaging have been realized with the introduction of state-of-the-art imaging equipment and radiopharmaceuticals. Gated tomographic myocardial perfusion imaging with technetium-99m (Tc-99m)-labeled radiopharmaceuticals provides a combined evaluation of both myocardial perfusion and function. Left ventricular ejection fraction can be measured accurately from the gated SPECT images. Recently, hardware and software have been introduced, which minimize the effect of soft tissue attenuation, thereby improving test specificity in the diagnosis of coronary artery disease. Myocardial viability may be assessed with the use of rest/delayed thallium-201 SPECT or F-18 fluorodeoxyglucose SPECT with modified scintillation camera collimation and electronics, or coincidence detection. Imaging patients to assess myocardial infarction or resting ischemia in the emergency department has expedited patient care and improved cost effectiveness. Teleradiography has also facilitated the interpretation of studies performed in the emergency department and at remote facilities, likewise improving cost-effectiveness.     

Imaging of transplanted islets by positron emission tomography,magnetic resonance imaging,and ultrasonography

While islet transplantation is considered a useful therapeutic option for severe diabetes mellitus (DM), the outcome of this treatment remains unsatisfactory. This is largely due to the damage and loss of islets in the early transplant stage. Thus, it is important to monitor the condition of the transplanted islets, so that a treatment can be selected to rescue the islets from damage if needed. Recently, numerous trials have been performed to investigate the efficacy of different imaging modalities for visualizing transplanted islets. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are the most commonly used imaging modalities for this purpose. Some groups, including ours, have also tried to visualize transplanted islets by ultrasonography (US). In this review article, we discuss the recent progress in islet imaging.     

Positron emission tomography imaging of regional pulmonary perfusion and ventilation

Positron emission tomography (PET) imaging is a noninvasive, quantitative method to assess pulmonary perfusion and ventilation in vivo. The core of this article focuses on the use of [13N]nitrogen (13N2) and PET to assess regional gas exchange. Regional perfusion and shunt can be measured with the 13N2-saline bolus infusion technique. A bolus of 13N2, dissolved in saline solution, is injected intravenously at the start of a brief apnea, while the tracer kinetics in the lung is measured by a sequence of PET frames. Because of its low solubility in blood, virtually all 13N2 delivered to aerated lung regions diffuses into the alveolar airspace, where it accumulates in proportion to regional perfusion during the apnea. In contrast, lung regions that are perfused but are not aerated and do not exchange gas (i.e., "shunting" units) do not retain 13N2 during apnea and the tracer concentration drops after the initial peak. Accurate estimates of regional perfusion and regional shunt can be derived by applying a mathematical model to the pulmonary kinetics of a 13N2-saline bolus. When breathing is resumed, specific alveolar ventilation can be calculated from the tracer washout rate, because 13N2 is eliminated almost exclusively by ventilation. Because of the rapid elimination of the tracer, 13N2 infusion scans can be followed by 13N2 inhalation scans that allow determination of regional gas fraction. This article describes insights into the pathophysiology of acute lung injury, pulmonary embolism, and asthma that have been gained by PET imaging of regional gas exchange.